The Molecular Cytogenetics Section of the Basic Research Laboratory is engaged in comparative chromosome mapping using fluorescence in situ hybridization (FISH).With the introduction of chromosome specific DNA probes, charting the genome and mapping chromosomal homology between species has became increasingly more rapid and economical. We employed fluorescence activated flow sorting (FACS) to sort chromosomes and construct chromosome specific DNA probes for humans and a number of species important in biomedical research (mouse, rat, various primates and domestic species such as the cat, pig, horse etc.). Reciprocal chromosome painting by fluorescence in situ hybridization between these species allows the transfer of gene mapping data thus aiding both disease and genetic trait analyses. The aim of this work is to define genes which are important in cancer in animal models, thus providing new insights into the role of chromosomes in human pathology and evolution. We demonstrated how modern molecular cytogenetics can literally dissect the evolution and origin of human chromosomes using an array of DNA probes of varying size. Intra-chromosomal rearrangements such as inversion and transpositions make up another set of plentiful and informative evolutionary changes of genome structure. We can study intra-chromosomal rearrangements by using probes derived from chromosome sub-regions with a resolution of 10-15 Mbp. We used a series of chromosome segment or even chromosome band specific probes to delineate the evolution of the human chromosome 3 and 21 in various mammals. The comparative map between these species allowed us to identify the history of these changes in various phylogenies. A further "dissection" of human chromosome evolution will finally allow us to construct large-scale comparative chromosome maps between placental mammals and perhaps other animals important in biomedical research.